LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model

This randomized, double-blind, placebo-controlled, crossover study (n=24) investigated the subjective effects of LSD (50 μg) and found significant overlap in the phenomenology of psychotic, mystical, and ego-dissolving experiences. The authors highlight the importance of meaning attribution to psychotic experiences in explaining how these different constructs converge in mystical experiences.


Background: For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience.

Methods: In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 μg d-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined.

Results: LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience.

Conclusions: The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences.

Authors: Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes, Amanda Feilding, Sidarta Ribeiro & Luís Fernando Tófoli


Research on LSD is notoriously multifaceted as scientists have characterized its subjective as either psychosis-like, mystical, or mind-revealing across various stages of its historic development. In fact, Humphrey Osmond who coined the term ‘psychedelic’ in conjunction with Aldous Huxley, sparked his interest in the substance upon noticing that it induces similar effects as the symptoms of schizophrenia. And although many researchers were interested in utilizing the mind-manifesting psychedelic properties of the substance to treat alcoholism and mood disorders, these research efforts were undercut by the cultural shift which propagated the myth that psychedelics can induce psychosis. Although this myth is largely discredited, the psychotomimetic model remains one of the most well-studied paradigms that compares the similarities and differences between psychedelics and psychosis (Geyer & Vollenweider, 2008).

As the word psychotomimetic implies, psychedelics mimic some of the most salient features of psychosis, such as altered perception of senses, self, body, time, altered emotions, impaired cognition, loss of intentionality, magical thinking, among others. But given the proximity of these symptoms to a state of psychosis, how is it that the same subjective effects take up such a central role within psychedelic-assisted psychotherapy? The current study sought to address this nuanced issue by examining how low-dose LSD (50 μg) occasions these experiences within the same cohort, in order to investigate the relationships that underly these different constructs within a randomized, double-blind, placebo-controlled, crossover study.

What did they measure?

  • Psychotic experiences were assessed within the model of aberrant salience, which is broadly defined as the process of placing inappropriate significance toexternal objects or internal representations, which gives rise to hallucinations and delusions in psychotic phenomena
  • Therapeutic potential was assessed by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ)
  • Psychedelic experiences were assessed assessed with four questionnaires: Altered State of Consciousness Questionnaire, Mystical Experiences Questionnaire, Challenging Experiences Questionnaire, and the Ego-Dissolution Inventory

What was the relationship between these experiences?

  • LSD-induced aberrant salience which highly correlated with altered state of consciousness, mystical experiences, and ego-dissolution
  • LSD increased suggestibility but not mindfulness

What does this reveal?

The results suggest that psychedelic and psychotic experiences share a mystical and ego-dissolution phenomenology. LSD spontaneously increased psychosis-like attributes to a greater extent than therapy-related aspects in the psychedelic experiences, which points to common mechanisms. LSD also increased suggestibility but not mindfulness, which indicates that substance does not have intrinsically therapeutic properties, but that therapeutic processes are engendered via therapeutic suggestion.

The authors also suggest a similar mechanism for LSD-induced aberrant salience, which might increase significance attribution and reduce ego boundaries and defence mechanisms, allowing for therapeutic changes in perspectives and attitudes. Hence the process of meaning attribution may elevate psychosis-like phenomena through therapeutic suggestions that foster mystical experiences.

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